TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32410	97453;97454;97455	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
N2AB	30769	92530;92531;92532	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
N2A	29842	89749;89750;89751	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
N2B	23345	70258;70259;70260	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
Novex-1	23470	70633;70634;70635	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
Novex-2	23537	70834;70835;70836	chr2:178542528;178542527;178542526	chr2:179407255;179407254;179407253
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-124
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.7528
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/E	None	None	0.001	N	0.095	0.042	0.168933306366	gnomAD-4.0.0	6.85687E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01534E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.1637	likely_benign	0.1379	benign	-0.627	Destabilizing	0.193	N	0.436	neutral	N	0.477685434	None	None	N
D/C	0.5734	likely_pathogenic	0.469	ambiguous	-0.049	Destabilizing	0.981	D	0.476	neutral	None	None	None	None	N
D/E	0.128	likely_benign	0.099	benign	-0.487	Destabilizing	0.001	N	0.095	neutral	N	0.452485883	None	None	N
D/F	0.6392	likely_pathogenic	0.5244	ambiguous	-0.575	Destabilizing	0.69	D	0.461	neutral	None	None	None	None	N
D/G	0.1792	likely_benign	0.1529	benign	-0.861	Destabilizing	0.193	N	0.419	neutral	N	0.467343087	None	None	N
D/H	0.2813	likely_benign	0.2255	benign	-0.651	Destabilizing	0.627	D	0.431	neutral	N	0.476724382	None	None	N
D/I	0.3624	ambiguous	0.28	benign	-0.044	Destabilizing	0.527	D	0.451	neutral	None	None	None	None	N
D/K	0.362	ambiguous	0.2915	benign	0.058	Stabilizing	0.241	N	0.419	neutral	None	None	None	None	N
D/L	0.3516	ambiguous	0.2774	benign	-0.044	Destabilizing	0.241	N	0.467	neutral	None	None	None	None	N
D/M	0.5251	ambiguous	0.4161	ambiguous	0.337	Stabilizing	0.944	D	0.436	neutral	None	None	None	None	N
D/N	0.1024	likely_benign	0.0873	benign	-0.281	Destabilizing	0.001	N	0.194	neutral	N	0.466836108	None	None	N
D/P	0.8873	likely_pathogenic	0.8451	pathogenic	-0.217	Destabilizing	0.818	D	0.447	neutral	None	None	None	None	N
D/Q	0.3002	likely_benign	0.241	benign	-0.249	Destabilizing	0.241	N	0.439	neutral	None	None	None	None	N
D/R	0.4154	ambiguous	0.341	ambiguous	0.155	Stabilizing	0.69	D	0.43	neutral	None	None	None	None	N
D/S	0.1081	likely_benign	0.0909	benign	-0.423	Destabilizing	0.241	N	0.434	neutral	None	None	None	None	N
D/T	0.1723	likely_benign	0.1414	benign	-0.239	Destabilizing	0.241	N	0.394	neutral	None	None	None	None	N
D/V	0.2225	likely_benign	0.1762	benign	-0.217	Destabilizing	0.001	N	0.299	neutral	N	0.501029192	None	None	N
D/W	0.8828	likely_pathogenic	0.8254	pathogenic	-0.403	Destabilizing	0.981	D	0.587	neutral	None	None	None	None	N
D/Y	0.2872	likely_benign	0.2308	benign	-0.336	Destabilizing	0.773	D	0.461	neutral	N	0.501830076	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.